A Vision for science

TabulaSynthase The blog of Whitehead Institute; bringing together ideas and perspectives from the Whitehead community and beyond.

Scientists use a variety of approaches to unravel the functions of organisms, cells, and even molecules, and some of these approaches produce images that are as stunning as they are informative.  Since 2011, the annual Koch Institute Image Awards, conducted by The Koch Institute for Integrative Cancer Research at MIT, has honored outstanding images created by life science and biomedical researchers in the MIT community.

This year, one of the winning pictures was created by Clare Harding, a postdoctoral researcher in the lab of Whitehead Institute Member and MIT assistant professor of biology, Sebastian Lourido. Harding and the other winners were lauded last night at a gala opening of the exhibit on the Koch building’s ground floor where the winning images will be on display for the coming year.

Whitehead has participated in this contest since its inception, with winning images by Gianluca De Rienzo (postdoctoral researcher in Whitehead Member Hazel Sive’s lab) in 2011, Rob Mathis (graduate student in Whitehead Member Piyush Gupta’s lab) in 2013, Daphne Superville (undergraduate student in Gupta’s lab) in 2015, Dexter Jin (graduate student in Gupta’s lab) in 2016, and Samuel A. LoCascio and Kutay Deniz Atabay (graduate students in Whitehead Member Peter Reddien’s lab) in 2017.

In Harding’s striking entry this year, each white and blue “petal” of the rosettes is a single-celled Toxoplasma gondii, the parasite that causes toxoplasmosis infection. This image was taken moments before the individual parasites comprising the daisy-like clusters would have triggered a massive, coordinated “egress”, which would destroy the host cell they had called home. The host’s nucleus is the large blue oblong jutting in from the upper left (host and parasite DNA are marked blue), and the red dapple marks a molecule in the host cell’s internal skeleton, called tubulin.

Toxoplasmosis infects about 25% of the world’s population and can cause serious disease in pregnant women, infants, and immunocompromised people. Not only is the Lourido lab’s work on T. gondii revealing important clues about this disease, but their research can also shed light on T. gondii’s close cousins on the evolutionary tree: Plasmodium spp., which cause malaria and contribute to more than a million deaths each year; and Cryptosporidium spp., which cause cryptosporidiosis, a gastrointestinal illness that can be fatal in those with a compromised immune system.

Harding’s research in the Lourido lab is focused on GAPM1a, a structural protein that forms a layer directly under T. gondii’s outer membrane and plays a similar architectural role in Plasmodium. This protein scaffold (marked as white in the image) is so vital that it is one of the first things established within daughter cells, which appear in the image as two small white spheres within some of the larger parasites. Parasites lacking the GAPM1a scaffold degrade into amorphous blobs that are unable to infect new host cells—a visual testament of how important this protein is to the parasites.

Light microscopy images like Harding’s are created by passing or reflecting light off of a sample and using one or more lenses to magnify the resulting representation. According to Wendy Salmon, the light microscopy specialist at Whitehead’s W.M. Keck Biological Imaging Facility and a two-time Koch Image Awards judge, all microscopy-based images are imperfect representations of the samples that they depict, because light microscopy is limited by the physics of the light shined on the sample and the glass that comprises the lenses. To push beyond the boundaries of physics and reveal the otherwise invisible, Harding employed two techniques: fluorescent markers and structured illumination microscopy.

Using a light microscope alone, the GAPM1a protein is indiscernible within T. gondii parasites.  But by genetically modifying the parasite to produce the GAPM1a protein fused to a green fluorescent protein, Harding could shine a particular wavelength of light onto the sample and cause the fluorescent protein to glow, thereby illuminating GAPM1a’s presence.

In addition to being able to identify the protein she is studying in a sample, Harding has the additional challenge that the parasites are so tiny—5 micrometers in length, or about 1/16th the width of a human hair—that they are beyond the resolution of light microscopy. In order to visualize the GAPM1a scaffold, Harding used a technique called structured illumination microscopy, which takes advantage of the properties of light in order to see things half the size of what is visible with a conventional light microscope. In this technique, the microscope casts a grid of light onto the specimen and takes images as the grid rotates. The resulting data from the images are processed using an algorithm that reconstructs the specimen’s appearance, enhancing its resolution.

Harding has been working with T. gondii for more than three years and microscopy has always played a major role in her work, but her appreciation for the science and art of microscopy has recently flourished.

“I like microscopy partly because it’s beautiful and partly because with a lot of other techniques, you need to interpret the data. With microscopy, you know what you’re looking at is right there,” says Harding, who is thrilled to have her work featured in the Koch Institute Public Galleries. “I definitely fell in love with microscopy right away. The first time I did it, I realized how much there is to a cell. Even just staining the DNA in a cell, suddenly you can see stars.”